Background: Ulcerative colitis is an intractable inflammatory colonic disease, and its etiology remains unclear. Saireito, a traditional herbal medicine, is widely used for treating ulcerative colitis in Japan. We analyzed the immunological characteristics of an oxazolone (OXZ)-induced colitis (OC) model and examined the effects of sareito on this model. Methods: OXZ was injected into the colon of BALB/c mice. Saireito was orally administered once a day for 3 consecutive days. Colitis was assessed by scoring the symptoms and macroscopic findings. The transcription patterns in the middle colon and spleen were analyzed with global transcriptome analysis and real-time polymerase chain reaction (PCR). Results: The above-mentioned scores were increased in the OC mice. The transcription levels of Th2 cytokines were significantly upregulated in the spleen and middle colon of the OC mice, whereas those of the Th1 cytokine interferon (IFN)-γ decreased in the spleen and increased in the middle colon. Saireito significantly ameliorated OC. In the middle colon of the saireito-treated mice, enhanced expression of Th2 cytokine mRNAs was markedly downregulated, while that of IFN-γ mRNA was further upregulated. In contrast, in the spleen, saireito had no effect on the transcription of either type of cytokine. After global transcriptome analysis, real-time PCR analysis revealed that saireito greatly downregulated the enhanced expression of the suppressor of cytokine signaling (SOCS)-3 mRNA in the middle colon of OC mice. Conclusions: Saireito exhibits inhibitory effects on OC by the induction of Th1-polarized immune responses in the mucosal immune system of the colon.